This Component is designed to provide a flexible means for developing and exploring new research activities or directions, and unique opportunities that can evolve into independently funded research projects. During Years 10-14, the Pilot Component funded 11 different projects; three projects (all new) will be funded in Year 15. Work conducted in these projects was instrumental in developing 4 successful federal research grants; several successful stimulus grant applications can also be traced directly or indirectly to pilot projects. One funded pilot has evolved into a new component (Grant) in this application. The Pilot Component has also been quite successful in attracting investigators new to alcohol research (Lattal, Kroenke, Low, Neve, Nagel, David and Allen). During Years 16-20, we propose to fund an average of 3 projects per year with an average budget of about $35K/project. The expected duration of these projects will be 1-3 years, with most lasting 1-2 years. The Center Scientific Director (Hitzemann) will manage this Component. Pilot Project applications will be solicited annually from local (primarily OHSU- and VAMC-based) investigators. Each proposal will be evaluated for scientific merit / innovation and for relatedness to the Center's overall goals by at least two members of the Center's Scientific Advisory Board, the Scientific Director, and the Center Director. Recommendations for funding will be considered for approval by the Center Executive Committee. Three new Projects are proposed for Year 16; all of these (10A, B and C) will cover project years 15 and 16 (assuming that significant progress warrants second year continuation). Three new projects (10D, E and F) will begin in year 17 and are expected to extend through year 18. Because we will continue each year to solicit new applications, the projects that are eventually funded may differ from those described here. Project 10-A (S. Murphy, PI) will examine the relationships among prenatal alcohol exposure, sex and stroke. Project 10-B (E. Boudreau, PI) will map brain changes in alcohol withdrawal using optical microangiography developed by the Co-I (R. Wang). Project 10-C (L. Sherman, PI) will examine the effects of ethanol exposure on hyaluronan-mediated adult neurogenesis as a potential mechanism contributing to alcoholic cognitive dysfunction. All three of these PIs are investigators new to alcohol research. Project 10-D (D. Rossi, PI) examines cellular mechanisms of alcohol use and withdrawal. Project 10-E (S. Mitchell, PI) is a clinical project that will examine the effects of alcohol on impulsivity and risk-taking in binge drinkers. Project 10-F (J. Crabbe, PI) will focus on alcohol tolerance and the transition from initial binge to chronic drinking in mice. Pilot Projects selected for funding during Years 18-20 are expected to contribute to the study of the behavioral genomics of alcoholism and the mechanisms underlying neuroadaptation to ethanol.